Gliederung

Background and aim: A recent meta-analysis of the US Food and Drug Administration (FDA) revealed that patients treated with antiepileptic drugs (AEDs) in randomized trials had a nearly doubled risk of suicidal thoughts and behaviour as compared with placebo. If all classes of AEDs increase the risk of suicidality remains, however, uncertain. Aim of our study was to investigate the risk of self harm or suicidal behaviour associated with the use of different classes of AEDs in patients with epilepsy.

Material and method: We performed a nested case-control study in a cohort of 44.300 patients with epilepsy who were treated with AEDs. Data were derived from the UK General Practice Research Database (GPRD). Patients with self harm or suicidal behaviour were identified by predefined codes. We included 453 cases and 8962 age- and sex-matched controls. AEDs were classified into 4 groups: barbiturates; conventional AEDs; newer AEDs with low (lamotrigine, gabapentin, pregabalin, oxcarbazepine) and with high (levetiracetam, tiagabine, topiramate, vigabatrin) potential of causing depression. Odds ratios (OR) were calculated using conditional logistic regression.

Results: Current use of newer AEDs with a high potential of causing depression was associated with a threefold increased risk of self harm/suicidal behaviour (OR=3.03; 95% CI 1.22–7.54) as compared with no use of AEDs during the last year. Use of barbiturates (OR=0.65; 95% CI 0.25–1.68), conventional AEDs (OR=0.73; 95% CI 0.54–0.97), or low risk newer AEDs (OR= 0.85; 95% CI 0.47–1.53) was not associated with an increased risk. Levetiracetam was the only individual AED associated with a significantly increased risk of self harm or suicidal behaviour.

Conclusions: Newer AEDs with a rather high frequency of depressive symptoms in clinical trials may also increase the risk of self harm or suicidal behaviour in clinical practice. For the most commonly used other AED classes, no increase in risk was observed.